Not more so than in the modern era of global travel has the potential catastrophic consequences of a pandemic arising from respiratory-borne pathogens been so acute. As such there is a striking need for quick and efficient large-scale vaccine production. Influenza virus poses a particular threat because of its capacity to evade the adaptive immune response by mutation. Furthermore, the existence of a sizeable animal reservoir in birds of influenza increases the chance of rapid emergence.
Influenza viruses continuously undergo antigenic variation (antigenic drift and antigenic shift) to evade the immune system of the host. The antigenic variation of influenza viruses forms the primary basis for the occurrence of annual influenza epidemics and occasional pandemics and necessitates constant evolution of vaccine composition. Existing vaccine production methods for influenza rely upon either use of embryonated eggs or cell culture, which are complex and time-consuming processes. Manufacture using these methods also requires specialized and costly infrastructure not widely available. In particular, the current lead time for initial delivery of even small amounts of influenza vaccine is several months following identification of a new pandemic strain. Clearly this amount of time is unacceptable in view of the estimated 1.2 billion high-risk people that will need rapid vaccination with the new and possibly as-yet-unknown vaccine in the event of an influenza pandemic. Further, the ideal method of pandemic prevention is initial containment of outbreaks by rapid vaccination of the entire population in the geographical risk region, not only high-risk young and old. This must occur rapidly and certainly faster than is possible using current vaccine biomanufacturing technologies. The issues of speed and scale are daunting considering the complexity and slowness of existing influenza vaccine technologies, and the need for specialized infrastructure.
Virus-like particles (VLPs) provide a potentially powerful tool in a number of applications including as vaccines, as vehicles for delivery of small molecules and in gene therapy. The potential efficacy of VLP-based vaccines has been postulated for some time and has been demonstrated for cervical cancer vaccines. It is thought that the particulate nature of VLPs induces a more effective immune response than denatured or soluble proteins as immunogens.
VLPs have the added advantage that at no stage during biomanufacture is an infectious virus created. This is distinct to existing embryonated egg technologies and some cell-culture technologies where (i) the starting point of manufacture is the creation of an infectious virus, necessitating high biocontainment during manufacture, and (ii) the virus may be disassembled during processing to remove infectivity (i.e. to reduce the possibility that the vaccine itself might cause disease). This disassembly process has the disadvantage that the virus structure is destroyed and consequently that less-effective denatured or soluble immunogens are administered.